A Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome

Fragile X Syndrome Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of BPN14770 in Male Adults (Aged 18 to 45) With Fragile X Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05358886
• Other study ID #: BPN14770-CNS-301
• Status: Recruiting
• Phase: Phase 3
• Start date: November 1, 2022
• Est. completion date: July 2024

Study information

• Verified date: February 2024
• Source: Tetra Discovery Partners
• Contact: CEO
• Phone: 616-224-0084
• Email: info[@]tetratherapeutics.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study of BPN14770 in Male Adults (Aged 18 to 45) with Fragile X Syndrome

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: July 2024
• Est. primary completion date: February 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

1. Male subject aged 18 to 45 years at screening visit.

2. Subject has FXS with a molecular genetic confirmation of the full fragile X mental retardation-1 (FMR1)mutation (=200 CGG repetitions).

3. Subject is able to swallow capsules.

4. Current treatment with =3 prescribed psychotropic medications. Anti-epileptic medications are permitted and are not counted as psychotropic medications if they are used for the treatment of seizures. Anti-epileptics for other indications, such as the treatment of mood disorders, count towards the limit of permitted medications.

5. Permitted concomitant psychotropic medications must be at a stable dose and dosing regimen for at least 4 weeks prior to screening and must remain stable during the period between screening and the commencement of the study treatment.

6. Anti-epileptic medications must be at a stable dose and dosing regimen for 12 weeks prior to screening and must remain stable during the period between screening and commencement of the study treatment.

7. Subjects with a history of seizure disorder who are currently receiving treatment with anti-epileptics must have been seizure free for 3 months preceding screening or must be seizure free for 2 years if not currently receiving anti-epileptics.

8. Behavioral and other non-pharmacological treatments/interventions must be stable for 4 weeks prior to screening and must remain stable during the period between screening and first dose of study treatment and throughout the study. Minor changes in hours or times of therapy that are not considered clinically significant will not be exclusionary. Changes in therapies provided through a program (eg, due to a vacation) are allowed.

9. Subject must be willing to practice barrier methods of contraception while on the study if sexually active. Abstinence is also considered a reasonable form of birth control in this study population.

10. Subject has a parent, legal authorized guardian, or consistent caregiver.

11. Subject and caregiver are able to attend the clinic regularly and reliably.

12. If subject is his own legal guardian, he is able to understand and sign informed consent to participate in the study.

13. For subjects who are not their own legal guardian, subject's parent/legally authorized guardian is able to understand and sign an informed consent form for their child to participate in the study.

14. If subject is not his own legal guardian, subject must provide assent for participation in the study if he has the cognitive ability to do so.

Exclusion Criteria:

1. Inability to successfully complete the NIH-TCB picture vocabulary and oral reading assessments at screening and baseline. The ability to complete the NIH-TBC oral reading and picture vocabulary subtest at baseline is defined as the ability to complete both subtests, with (1) confirmation from the clinician administering that the test administrations are valid (noted on the administration form) and (2) generation of valid test scores for each test.

2. History of or current cardiovascular, renal, hepatic, respiratory, gastrointestinal, psychiatric, neurologic, cerebrovascular, or other systemic disease that would place the subject at risk or potentially interfere with the interpretation of the safety, tolerability, or efficacy of the study treatment.

a. Common conditions such as mild hypertension, etc. are allowed per the principal investigator's judgement as long as they are stable and controlled by medical therapy that is constant for at least 4 weeks before randomization.

3. Renal impairment, defined as serum creatinine > 1.25 × ULN at screening

4. Hepatic impairment, defined as ALT or AST elevation > 2 × ULN at screening. Note: LFTs may be repeated after 1 week to evaluate return to acceptable limits; if LFTs remain elevated, the subject is ineligible to participate.

5. Clinically significant abnormalities, in the investigator's judgement, in safety laboratory tests, vital signs, or ECG, as measured during screening.

6. History of substance abuse within the past year, according to investigator assessment.

7. Positive COVID-19 test during screening.

8. Significant hearing or visual impairment that may affect the subject's ability to complete the test procedures.

9. Concurrent major psychiatric condition (eg, major depressive disorder, schizophrenia, or bipolar disorder) as diagnosed by the investigator. Subjects with the additional diagnosis of autism spectrum disorder or anxiety disorder will be allowed.

10. Subject has active diseases that would interfere with participation, such as acquired immunodeficiency disorder, hepatitis C, hepatitis B, or tuberculosis.

11. Subject is planning to commence psychotherapy or cognitive behavior therapy during the period of the study or had begun psychotherapy or cognitive behavior therapy within 4 weeks prior to screening.

12. Subject is an immediate family member of anyone employed by the sponsor, investigator, or study staff.

13. Subject has a body mass index of less than 18 kg/m2 or greater than 36 kg/m2.

14. Subject has participated in another clinical trial within the 30 days preceding Screening

Related Conditions & MeSH terms

• Fragile X Syndrome
• Syndrome

Intervention

Drug:
• BPN14770/ zatolmilast
25mg BID BPN14770
• Placebo
Placebo

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Kennedy Krieger Institute	Baltimore	Maryland
United States	Rush University Medical Center	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital Colorado	Denver	Colorado
United States	Amnova Clinical Research	Irvine	California
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Suburban Research Associates	Media	Pennsylvania
United States	Icahn School of Medicine at Mount Sinai Hospital	New York	New York
United States	CHOC Thompson Autism Center	Orange	California
United States	UC Davis Health System	Sacramento	California
United States	Clinic for Special Children	Strasburg	Pennsylvania
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Tetra Discovery Partners

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	National Institutes of Health Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC)	National Institutes of Health Toolbox Cognitive Battery cognition crystallized composite score (NIH-TCB CCC), which is calculated from the Picture Vocabulary and Oral Reading domains.	13 Weeks
Secondary	Numerical rating scale (NRS) scores based on subject-specific behaviors vs baseline	Numerical rating scale (NRS) scores based on subject-specific behaviors within the domains of Daily Function and Language	13 Weeks
Secondary	Caregiver Global Impression of Improvement (CaGI-I)	Caregiver Global Impression of Improvement (CaGI-I) for the general domains of Daily Function and Language	13 Weeks
Secondary	Clinical Global Impression Improvement (CGI-I) for - Investigator	Clinical Global Impression Improvement (CGI-I) for - Investigator rated the general domains of Daily Function and Language	13 Weeks
Secondary	Vineland-3 Adaptive Behavior Scale (Vineland-3)	Vineland-3 Adaptive Behavior Scale (Vineland-3), using the composite score and domain scores from communication, daily living skills, and socialization	13 Weeks
Secondary	Verbal Knowledge test from the Stanford-Binet (ed 5) (SB-5)IQ	Verbal Knowledge test from the Stanford-Binet (ed 5) (SB-5) IQ assessment	13 Weeks
Secondary	NIH-TCB domains of Picture Sequence Memory, Flanker Inhibitory Control and Attention, List Sorting Working Memory, Dimensional Change Card Sort, and Speeded Matching	NIH-TCB domains of Picture Sequence Memory, Flanker Inhibitory Control and Attention, List Sorting Working Memory, Dimensional Change Card Sort, and Speeded Matching	13 Weeks
Secondary	Aberrant Behavior Checklist (ABC) scores	Aberrant Behavior Checklist (ABC) scores	13 Weeks
Secondary	Anxiety, Depression, and Mood Scale (ADAMS) scores	Anxiety, Depression, and Mood Scale (ADAMS) scores	13 Weeks